In vivo and rapid procedures for tissue diagnosis are important for efficient cancer detection and therapy. As an example of one type of detection, endoscopy is used to detect abnormal tissues in the human esophagus. Once an abnormality is found, biopsies are taken for determination of histopathology.
For diagnosis, a biopsy sample usually represents a very small area. The laboratory results are generally not available for several days. Thus, the known endoscopic techniques do not provide real-time in vivo classification of the tissue type.
Recently there has been interest in using laser-induced fluorescence (LIF) in the development of diagnostic and therapeutic tools. A number of investigators have used LIF as a method to discriminate tumors from normal tissues. For example, The LIF technique has been used to distinguish adenomatous polyps from normal colon tissue and hyperplastic polyps in vitro. See C. R. Kapadia et al., "Laser-Induced Fluorescence Spectroscopy of Human Colonic Mucosa--Detection of Adenomatous Transformation," Gastroenterology, 99: 150-157 (1990) .
Still others have investigated the LIF technique to distinguish adenomatous tissue from normal colon tissue in vivo. See R. M. Cothren et al., Gastrointestinal Tissue Diagnosis By Laser-Induced Fluorescence Spectroscopy at Endoscopy," Gastrointestinal Endoscopy, 36: 105-111, (1990). Fluorescence techniques have also been used to characterize normal and malignant breast tissues, lung tissues, and to quantify photodynamic therapy drugs in rat tissues. A fiber optic LIF antibody-based biosensor has been used to detect DNA modification by carcinogenic chemicals in human placenta samples.
Other investigators have used LIF and multivariate linear regression analysis to distinguish neoplastic tissue from non-neoplastic tissue. See K. T. Schomacker et al., Ultraviolet Laser-Induced Fluorescence of Colonic Tissue: Basic Biology and Diagnostic Potential," Lasers In Surgery and Medicine, 12: 63-68 (1992).
The Schomacker et al. data suggest that the LIF measurements detected changes in polyp morphology rather than changes in fluorosphores specific to polyps, and it was this change in morphology that leads indirectly to discrimination of polyps. Schomacker et al. concluded that the feasibility of discriminating groups of normal from dysplastic cells by LIF is as yet undemonstrated.
U.S. Pat. No. 4,930,516 to Alfano et al. describes a method for detecting cancerous tissue using laser-induced fluorescence. The wavelengths at which maximum intensities are attained for sample tissue are determined and compared to peak wavelengths derived from known non-cancerous tissue.
U.S. Pat. No. 5,131,398 to Alfano et al. describes a method of distinguishing cancerous tissue from benign tumor tissue using a light source which produces a 300-nm monochromatic light beam which is directed into the sample through an endoscope. Emission radiation produced by fluorescence is measured at 340 and 440 nm, and a ratio of the two intensities is then calculated and used as a basis for determining if the tissue is cancerous.
A further endoscopic technique is described in U.S. Pat. No. 5,261,410 to Alfano et al. uses an infrared monochromatic light source, and then measures the Raman shift in emission radiation to ascertain the condition of a tissue sample.
The foregoing references and studies detailed therein indicate that there remains a strong need to develop improved procedures for effective cancer diagnosis.